Towards the identification of a mesoscale neural systems logic underlying innate behaviors

识别先天行为背后的中尺度神经系统逻辑

基本信息

批准号：
10734660
负责人：
Stefanos Stagkourakis
金额：
$ 12.21万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734660
关键词：
Address Affect Aggressive behavior Amygdaloid structure Anatomy Animals Anterior Area Award Behavior Behavior Control Behavioral Behavioral Paradigm Brain Brain imaging Brain region Cell Nucleus Chronic Cognition Communication Complement Computer software Custom Data Development Discipline Electrophysiology (science)Emotional Exhibits FOS gene Female Financial Hardship Fluoxetine Fright Goals Grain Human Hypothalamic structure Image Instinct Investigation Laboratory mice Learning Logic Maps Measurement Medical Mental disorders Mentors Methodology Methods Molecular Monitor Mus Neurons Neurosciences Partner in relationship Pattern Phase Physiological Population Prefrontal Cortex Prevalence Reagent Research Resolution Risperidone Role Sex Offenses Shapes Silicon Social isolation Societies Spatial Distribution System Technology Testing Therapeutic Training Vision Work activity marker analysis pipeline behavior influence behavior prediction behavioral plasticity cell type cognitive process conditioned fear design experience experimental study extracellular family burden frontier generalized anxiety in vivo insight interest machine learning method male neural new technology novel novel therapeutics pharmacologic predictive modeling programs response segregation skills social theories therapeutically effective tool

项目摘要

Project Summary/Abstract Innate behaviors, also known as instincts, are essential for the survival of all species in the animal kingdom, including humans. Of great interest is understanding how the experience-induced behavioral plasticity observed in innate behaviors can lead to maladaptive behavioral expressions, including uncontrolled aggression, sex offenses, and generalized anxiety. Such mental disorders carry a substantial emotional and financial burden to families and society, rendering the development of effective therapeutic approaches of high significance. The neural substrates of innate behaviors are distributed across numerous brain regions. An essential step towards understanding how the brain orchestrates behavior is to identify how inter-region interactions of neural activity influence behavior in freely moving animals. However, methodological limitations have largely restricted such investigations to single nuclei, while the deep brain remains to date inaccessible to in vivo mesoscale neural recordings in freely moving animals. The research proposed here uses custom-designed technology to break this methodological barrier, making possible recordings with single-unit resolution across twenty subregions of the deep brain (hypothalamus) in freely moving, innate behavior-expressing mice. In Aim 1, using this technology, I will investigate the presence of behavior-specific mesoscale hypothalamic neural features in the innate and learned expressions of social and fear-related behaviors. I will test whether the activity of specific brain regions can predict specific behaviors, and I will identify the spatial distribution of hypothalamic clusters exhibiting behavior-tuning or mixed selectivity. In Aim 2, I will dissect how aggression- or fear-conditioning alters mesoscale neural activity dynamics and test the effect of chronic administration of pharmacological reagents known to reduce the expression of maladaptive social and fear behaviors. Lastly, in Aim 3 – the independent phase of the award, I will expand the use of these tools to investigate mesoscale neural activity dynamics across diverse areas of the corticolimbic system, seeking to identify local and global principles that guide the expression of the physiological and maladaptive forms of innate behaviors. Collectively, the above approaches target the development of an experimental and analytical platform to address fundamental questions of systems neuroscience on the mesoscale mechanisms that govern the expression of innate behaviors. Following these initial steps, this work will be complemented by experimentation aiming to test whether the identified neural features in the behaviors of interest have a causal role. Through the mentored phase of this award, my vision is to build a highly complementary skillset to the one I acquired during my graduate training, and create a unique, state-of-the-art independent research program. By pursuing work spanning diverse disciplines, including molecular, cellular, systems neuroscience, behavioral and computational approaches, I am committed to developing a mechanistic understanding of the neural basis of innate behaviors, with the potential to lead to advanced therapeutic solutions.

项目摘要/摘要先天行为，也称为本能，对于动物界所有物种的生存至关重要，包括人类。非常有趣的是了解如何观察到经验引起的行为可塑性在先天行为中，可能导致适应不良的行为表达，包括不受控制的侵略性，性别犯罪和广义动画。这种精神障碍会造成大量的情感和经济上的燃烧家庭和社会，发展出高意义的有效治疗方法。先天行为的神经底物分布在众多大脑区域。重要的一步要了解大脑如何策划行为是确定神经元间相互作用的方式活动会影响自由移动动物的行为。但是，方法上的局限性在很大程度上受到限制这样的单个核的投资，而深度大脑仍然无法进入体内中性自由移动动物的录音。这里提出的研究使用定制设计的技术破坏这种方法论障碍，通过二十个子区域的单单元分辨率使可能的记录。自由移动的，天生的表达小鼠的深脑（下丘脑）。在AIM 1中，使用该技术，我将研究特定于行为特定的中层丘脑的存在与生俱来的和学到的与社会和恐惧相关的行为的表达中的神经特征。我将测试是否特定大脑区域的活动可以预测特定的行为，我将确定下丘脑簇表现出行为调节或混合选择性。在AIM 2中，我将剖析如何具有侵略性或恐惧条件改变了中尺度的神经活动动态，并测试长期给药的影响已知可减少适应不良的社会和恐惧行为表达的药理试剂。最后，在 AIM 3 - 奖项的独立阶段，我将扩大这些工具的使用来调查中立中性跨皮质胶体系统的潜水区域的活动动态，旨在识别本地和全球原则它指导了先天行为的身体和适应不良形式的表达。总的来说，上述方法针对的是开发实验和分析平台解决系统神经科学的基本问题天生行为的表达。遵循这些初始步骤，这项工作将通过实验完成旨在测试感兴趣的行为中确定的神经特征是否具有因果作用。通过该奖项的修订阶段，我的愿景是为我建立一个高度完整的技能在我的研究生培训期间获得，并创建了一个独特的，最先进的独立研究计划。经过追求跨越潜水学科的工作，包括分子，细胞，系统神经科学，行为和行为和计算方法，我致力于建立对神经基础的机械理解先天的行为，有可能导致先进的治疗解决方案。